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Chronic Lymphocytic LeukemiaPhase 1NCT03892044

Duvelisib and Nivolumab in Treating Patients With Richter Syndrome or Transformed Follicular Lymphoma

A Phase 1 study testing Duvelisib and Nivolumab in people with Chronic Lymphocytic Leukemia and Recurrent Diffuse Large B-Cell Lymphoma, run by David Bond, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of duvelisib when given together with nivolumab in treating patients with Richter syndrome or transformed follicular lymphoma. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Duvelisib and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
5 Nov 2019to 14 Feb 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of CLL or small lymphocytic lymphoma (SLL) meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria AND biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), clinically consistent with Richter?s syndrome (RS) OR histologically diagnosed relapsed or refractory DLBCL including transformed follicular lymphoma (tFL) ineligible for or refractory to platinum containing salvage therapy for the dose escalation portion of the study. For the dose expansion phase only patients with CLL with transformation to DLBCL or tFL will be eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 500/uL
  • Platelet count >= 30,000/uL (unless due to bone marrow involvement)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 ULN
  • Total bilirubin =< 1.5 ULN (unless due to liver involvement, hemolysis, or Gilbert?s disease)
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  • Creatinine clearance >= 40 mL/min (Cockcroft-Gault estimated)
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Patients must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study

Who cannot join

  • Documented infection with human immunodeficiency virus (HIV) or chronic, active hepatitis B or C infection
  • Any chemotherapy or monoclonal antibodies within 14 days or kinase inhibitors (except BTKi) within 5 half-lives before cycle 1, day 1 (C1D1). BTK inhibitors may be continued until 2 days prior to C1D1. Steroids are allowed for palliation of symptoms due to lymphoma
  • Toxicity from previous therapy which has not resolved to grade 1 (or patient?s previous baseline)
  • Other active malignancies except those treated with curative intent with no active disease at the time of study entry or those felt to be at low risk of progression or recurrence over the next 2 years (such as low risk prostate cancer on active surveillance)
  • New York Heart Association (NYHA) class III/IV heart disease or other significant medical condition or organ system dysfunction which could compromise the subject?s safety or put the study outcomes at undue risk
  • Uncontrolled systemic infection
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  • Unable to swallow capsules or significant malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction at the time of screening
  • Patients who are pregnant or breastfeeding
  • Patients with known central nervous system (CNS) involvement by CLL or lymphoma
  • Patients who have underwent autologous or allogeneic stem cell transplant =< 4 weeks prior to C1D1 or have active graft-versus-host disease are excluded

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Study of Duvelisib in Combination With Nivolumab for Patients With Richter's Syndrome and Transformed Follicular Lymphoma

This phase I trial studies the side effects and best dose of duvelisib when given together with nivolumab in treating patients with Richter syndrome or transformed follicular lymphoma. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving duvelisib and nivolumab may work better in treating patients with Richter syndrome or transformed follicular lymphoma compared to giving duvelisib or nivolumab alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated dose (MTD) of duvelisib in combination with nivolumab for patients with Richter?s syndrome or transformed follicular lymphoma.

SECONDARY OBJECTIVES:

  1. To assess preliminary efficacy of duvelisib in combination with nivolumab in Richter?s syndrome and transformed follicular lymphoma (overall response rate, progression free survival, overall survival).

II. To determine the toxicity profile of duvelisib in combination with nivolumab.

EXPLORATORY OBJECTIVES:

  1. To correlate response to duvelisib in combination with nivolumab with cytogenetic/fluorescence in-situ hybridization (FISH) abnormalities of the chronic lymphocytic leukemia (CLL) and lymphoma compartments (for patients with Richter?s syndrome) at baseline.

II. To correlate response to duvelisib in combination with nivolumab with baseline deoxyribonucleic acid (DNA) mutation of CLL and lymphoma as assessed in tumor samples and cell free DNA.

III. To determine changes in T, B, and natural killer (NK) cell number and function during duvelisib plus nivolumab therapy.

OUTLINE: This is a dose-escalation study of duvelisib.

Patients receive duvelisib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter.

Being tested
Duvelisib, Nivolumab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DuvelisibDrug

    Also called 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, INK-1197, IPI-145

    Given PO

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT03892044
Study groupRoleWhat they receive
Treatment (duvelisib, nivolumab)ExperimentalPatients receive duvelisib PO BID on days 1-28 and nivolumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Duvelisib; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum-tolerated dose (MTD) of duvelisib

    The MTD is defined as the highest dose level where at most one patient out of six experiences dose-limiting toxicities.

    Measured: Up to 28 days

Secondary outcomes (3)

  1. Overall response rate

    Will be defined as the proportion of patients achieving a complete or partial response; any eligible patient who begins treatment with the combination regimen will be included in the denominator. Will be calculated with a 95% binomial confidence interval.

    Measured: Up to 3 years

  2. Progression-free survival (PFS)

    The method of Kaplan Meier will be used to estimate PFS.

    Measured: From cycle 1, day 1 to date of progression or death, assessed up to 3 years

  3. Overall survival (OS)

    The method of Kaplan Meier will be used to estimate OS.

    Measured: From cycle 1, day 1 to date of progression or death, assessed up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2019
  2. Study start5 Nov 2019
  3. Primary completion14 Feb 2024
  4. Study completion14 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03892044
Sponsor's protocol ID
OSU-18173
Other IDs
NCI-2019-01028
Status last verified
Apr 2024
First submitted
25 Mar 2019
Last updated
2 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Iannello A, Vitale N, Coma S, Arruga F, Chadburn A, Di Napoli A, Laudanna C, Allan JN, Furman RR, Pachter JA, Deaglio S, Vaisitti T. Synergistic efficacy of the dual PI3K-delta/gamma inhibitor duvelisib with the Bcl-2 inhibitor venetoclax in Richter syndrome PDX models. Blood. 2021 Jun 17;137(24):3378-3389. doi: 10.1182/blood.2020010187.

    PubMed 33786583

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Duvelisib and Nivolumab in people with Chronic Lymphocytic Leukemia and Recurrent Diffuse Large B-Cell Lymphoma, run by David Bond, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum-tolerated dose (MTD) of duvelisib (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03892044, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.

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